Efficacy and Safety of Efpeglenatide Versus Placebo in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Basal Insulin Alone or in Combination With Oral Antidiabetic Drug(s) (AMPLITUDE-L)

A 56-week, Multicenter, Double-blind, Placebo-controlled, Randomized Study to Evaluate the Efficacy and Safety of Efpeglenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Basal Insulin Alone or in Combination With Oral Antidiabetic Drug(s)

Primary Objective:

To demonstrate the superiority of once weekly injection of efpeglenatide in comparison to placebo in glycated hemoglobin (HbA1c) change in participants with type 2 diabetes mellitus (T2DM) inadequately controlled with basal insulin alone or in combination with oral antidiabetic drugs (OADs).

Secondary Objectives:

• To demonstrate the superiority of once weekly injection of efpeglenatide in comparison to placebo on glycemic control.
• To demonstrate the superiority of once weekly injection of efpeglenatide in comparison to placebo on body weight.
• To evaluate the safety of once weekly injection of efpeglenatide.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: Background therapy; Drug: Efpeglenatide SAR439977

Detailed Description

Study duration per participant was approximately 64 weeks including an up to 2-week Screening Period, a 30-week Core Treatment Period, a 26-week Safety Extension Period, and a 6-week safety Follow-up Period.

• Study Type: Interventional
• Enrollment (Actual): 370
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Baotou, China, 014010
    • Investigational Site Number 1560005
  • Beijing, China, 100730
    • Investigational Site Number 1560017
  • Changsha, China, 410013
    • Investigational Site Number 1560006
  • Chengdu, China, 610083
    • Investigational Site Number 1560001
  • Shanghai, China, 014010
    • Investigational Site Number 1560004
  • Shanghai, China, 200032
    • Investigational Site Number 1560036
  • Shanghai, China, 200040
    • Investigational Site Number 1560012
  • Shanghai, China, 200040
    • Investigational Site Number 1560013
  • Zhengzhou, China, 450003
    • Investigational Site Number 1560003
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Investigational Site Number 4100009
  • Daejeon, Korea, Republic of, 35233
    • Investigational Site Number 4100001
  • Gwangju, Korea, Republic of, 501757
    • Investigational Site Number 4100016
  • Gwangju, Korea, Republic of, 61453
    • Investigational Site Number 4100010
  • Gyeonggi-do, Korea, Republic of, 11765
    • Investigational Site Number 4100013
  • Incheon, Korea, Republic of, 21565
    • Investigational Site Number 4100015
  • Jeonju, Korea, Republic of, 54907
    • Investigational Site Number 4100014
  • Seongnam-Si, Korea, Republic of, 13620
    • Investigational Site Number 4100007
  • Seoul, Korea, Republic of, 03080
    • Investigational Site Number 4100002
  • Seoul, Korea, Republic of, 02447
    • Investigational Site Number 4100008
  • Seoul, Korea, Republic of, 03722
    • Investigational Site Number 4100005
  • Seoul, Korea, Republic of, 05278
    • Investigational Site Number 4100004
  • Seoul, Korea, Republic of, 06351
    • Investigational Site Number 4100003
  • Seoul, Korea, Republic of, 07345
    • Investigational Site Number 4100011
  • Seoul, Korea, Republic of, 14647
    • Investigational Site Number 4100006
  • Suwon, Korea, Republic of, 16247
    • Investigational Site Number 4100012
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Investigational Site Number 8400038
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Investigational Site Number 8400035
    • Glendale, Arizona, United States, 85306
      • Investigational Site Number 8400005
  • California
    • Huntington Park, California, United States, 90255
      • Investigational Site Number 8400057
    • La Jolla, California, United States, 92037
      • Investigational Site Number 8400058
    • Los Angeles, California, United States, 90057
      • Investigational Site Number 8400009
    • Spring Valley, California, United States, 91978
      • Investigational Site Number 8400045
    • Tustin, California, United States, 92780
      • Investigational Site Number 8400040
    • Van Nuys, California, United States, 91405
      • Investigational Site Number 8400026
  • Florida
    • Orlando, Florida, United States, 32825
      • Investigational Site Number 8400055
    • Pembroke Pines, Florida, United States, 33026
      • Investigational Site Number 8400041
  • Georgia
    • Lawrenceville, Georgia, United States, 30044
      • Investigational Site Number 8400025
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Investigational Site Number 8400052
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Investigational Site Number 8400044
  • New Jersey
    • Bridgeton, New Jersey, United States, 08302
      • Investigational Site Number 8400001
  • New York
    • New Windsor, New York, United States, 12553
      • Investigational Site Number 8400039
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Investigational Site Number 8400036
  • Ohio
    • Maumee, Ohio, United States, 43537
      • Investigational Site Number 8400013
  • Texas
    • Dallas, Texas, United States, 75230
      • Investigational Site Number 8400030
    • Dallas, Texas, United States, 75390-9302
      • Investigational Site Number 8400063
    • San Antonio, Texas, United States, 78229
      • Investigational Site Number 8400043
  • Utah
    • Layton, Utah, United States, 84041
      • Investigational Site Number 8400037

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Participant must be greater than or equal to (>=)18 years of age at the time of signing the informed consent.
• Participants with T2DM.
• Diabetes diagnosed at least 1 year before screening.
• Participants on basal insulin regimen alone or in combination with OADs for at least 6 months prior to screening.
• HbA1c between 7.0 percent (%) and 10.0% (inclusive) measured by the central laboratory at screening.

Exclusion criteria:

• History of severe hypoglycemia requiring emergency room admission or hospitalization within 3 months prior to screening.
• Retinopathy or maculopathy with one of the following treatments, either recent (within 3 months prior to screening) or planned: intravitreal injections or laser or vitrectomy surgery.
• Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to) gastroparesis, unstable and not controlled gastroesophageal reflux disease requiring medical treatment within 6 months prior to screening.
• History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy has been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy.
• Personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (e.g., multiple endocrine neoplasia syndromes).
• Body weight change of >=5 kilograms within the last 3 months prior to screening.
• Systolic blood pressure greater than (>)180 millimetres of mercury (mmHg) and/or diastolic blood pressure >100 mmHg at randomization.
• End-stage renal disease as defined by estimated glomerular filtration rate (by Modification of Diet in Renal Disease) of less than 15 mL/min/1.73 m^2.

• Laboratory findings at the screening Visit:

  • Alanine aminotransferase or aspartate aminotransferase >3 * upper limit of normal (ULN) or total bilirubin >1.5*ULN (except in case of documented Gilbert's syndrome);
  • Amylase and/or lipase: >3*ULN;
  • Calcitonin >=5.9 picomoles per liter (pmol/L) (20 picograms per milliliter [pg/mL]).
• Gastric surgery or other gastric procedures intended for weight loss within 2 years prior to screening, or planned during study period.
• Pregnant (confirmed by serum pregnancy test at screening) or breast-feeding women.
• Women of childbearing potential not willing to use highly effective method(s) of birth control or who were unwilling to be tested for pregnancy during the study period and for at least 5 weeks after the last dose of study intervention.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Participants received placebo (matched to efpeglenatide) subcutaneous (SC) injection once weekly up to Week 56 on top of basal insulin alone or in combination with oral antidiabetic drugs (OADs).	Drug: Placebo; Pharmaceutical form: solution for injection Route of administration: subcutaneous; Drug: Background therapy; Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.
EXPERIMENTAL: Efpeglenatide 2 mg; Participants received Efpeglenatide 2 milligrams (mg) SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs.	Drug: Background therapy; Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.; Drug: Efpeglenatide SAR439977; Pharmaceutical form: solution for injection Route of administration: subcutaneous
EXPERIMENTAL: Efpeglenatide 4 mg; Participants received Efpeglenatide 4 mg SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg and maintained at the 4 mg dose through-out the treatment duration up to Week 56.	Drug: Background therapy; Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.; Drug: Efpeglenatide SAR439977; Pharmaceutical form: solution for injection Route of administration: subcutaneous
EXPERIMENTAL: Efpeglenatide 6 mg; Participants received Efpeglenatide 6 mg SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg until Week 4 and later up-titrated to 6 mg and maintained at the 6 mg dose through-out the treatment duration up to Week 56.	Drug: Background therapy; Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.; Drug: Efpeglenatide SAR439977; Pharmaceutical form: solution for injection Route of administration: subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline to Week 30 in HbA1c	Baseline to Week 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With HbA1c <7.0% at Week 30	Participants who had no available assessment for HbA1c at Week 30 were considered as non-responders.	Week 30
Change From Baseline to Week 56 in HbA1c	This analysis included Week 56 assessment performed per protocol as well as premature end of treatment/study visit recorded as Week 56 due to early termination.	Baseline to Week 56
Change From Baseline to Week 30 in Fasting Plasma Glucose (FPG)		Baseline to Week 30
Change From Baseline to Week 30 and Week 56 in Body Weight	This analysis included Week 56 assessment performed per protocol as well as premature end of treatment/study visit recorded as Week 56 due to early termination.	Baseline to Week 30 and Week 56
Number of Participants With At Least One Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL], and Severe Hypoglycemia)	Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <54 mg/dL (<3.0 mmol/L). Severe hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.	Baseline up to Week 56
Number of Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL] and Severe Hypoglycemia) Per Participant-Year	Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <54 mg/dL (<3.0 mmol/L). Severe hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.	Baseline up to Week 56

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Hanmi Pharmaceutical Company Limited

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 9, 2018
• Primary Completion (ACTUAL): November 20, 2020
• Study Completion (ACTUAL): January 4, 2021

Study Registration Dates

• First Submitted: October 18, 2018
• First Submitted That Met QC Criteria: October 18, 2018
• First Posted (ACTUAL): October 22, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 2, 2021
• Last Update Submitted That Met QC Criteria: November 4, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Efpeglenatide
• Other Study ID Numbers: EFC14893; U1111-1189-5009 (OTHER: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share individual participant data (IPD) by SANOFI: Product rights transferred to Hanmi Pharmaceutical.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No